Biogen Inc. scientists and colleagues have reported theengineering of a "humanized" immunotoxin, a hybrid moleculethat uses antibodies to specifically guide a toxin into cancercells.
In the current issue of the Proceedings of the NationalAcademy of Sciences, the researchers described theconstruction of a chimeric gene that codes both for a guidingantibody and for an enzyme to kill tumors. Cultures of cellsengineered to express the gene construct secreted theimmunotoxin, which was demonstrated to inhibit growth ofcancer cells.
National Institutes of Health researchers, collaborating with aBelgian scientist and with Biogen, used a human protein, calledangiogenin, for the toxin. The scientists predicted that"humanization of immunotoxins will lead to less (bodywide)toxicity" and will be less likely to provoke unwanted immunereactions.
The NIH researchers previously had used the RNase enzymefrom cows as an alternative to toxins from plants or bacteria.Human angiogenin has similar actions to cow RNase, and alsoinhibits protein synthesis, necessary for any cell's survival.Although angiogenin is not usually toxic to cells, it wouldbecome destructive if it could enter cells.
The chimeric construct attached angiogenin to an antibodymolecule that allowed entry specifically into cancer cells.
-- Roberta Friedman, Ph.D. Special to BioWorld
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